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Bone and haematopoietic defects in mice lacking c-fos

Abstract

THE proto-oncogene c-fos is the cellular homologue of v-fos originally isolated from murine osteosarcoma1. Fos protein is a major component of the AP-1 transcription factor complex, which includes members of the jun family2. Stable expression of c-fos in mice has been demonstrated in developing bones and teeth, haematopoietic cells, germ cells and in the central nervous system3–11. It has been proposed that c-fos has an important role in signal transduction, cell proliferation and differentiation12–15. We have previously demonstrated that overexpression of c-fos in transgenic and chimaeric mice specifically affects bone, cartilage and haematopoietic cell development16–20. To understand better the function of c-fos in vivo, we used gene targeting in embryonic stem cells to generate cells and mice lacking c-fos. Here we report that heterozygous fos +/− mice appear normal, although females exhibit a distorted transmission frequency. All homozygous fos −/− mice are growth-retarded, develop osteopetrosis with deficiencies in bone remodelling and tooth eruption, and have altered haematopoiesis. These data define the c-Fos protein as an essential molecule for the development of specific cellular compartments.

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Wang, ZQ., Ovitt, C., Grigoriadis, A. et al. Bone and haematopoietic defects in mice lacking c-fos. Nature 360, 741–745 (1992). https://doi.org/10.1038/360741a0

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